The interior has walls of cream-coloured Tymawr brick, with Bute red and Staffordshire blue brick employed in bands, patterning and relieving arches. The 2-bay nave and transepts have arched-brace roofs with a single tier of wind braces and pierced arcading above the cornice. The principals stand on short wall shafts with head corbels, except the N transept which has an angel corbel to the central principal on the N side. The nave W window has a shafted rere arch with hood mould and head stops. The transepts have N and S windows with linked hood moulds that form an impost band with blind cusped arch to the centre, while the sexfoil windows have a moulded sill band, shafted rere arch and hood mould.
The broad crossing has 2-centred arches to the nave and transepts with cylindrical responds to the transepts and on round corbels to the nave, and all with foliage capitals. The piers are composed of banded polychrome masonry including white Bridgend stone, Red Radyr stone, grey-green Forest of Dean stone and alabaster. The SW pier has a 1914-18 war memorial inscription. The crossing retains squinches (for Prichard's intended octagonal tower) and a panelled wooden ceiling on corbels, the main ribs having nail-head moulding, the subsidiary ribs plainer mouldings. The 2-centred chancel arch forming the E side of the crossing is more elaborate than the other arches. It has shafts, the abaci of which support pairs of subsidiary shafts with waterleaf capitals to the inner orders, and head corbels to the outer order.
The chancel has a boarded, keeled wagon roof with thin ribs and bosses. The walls have richer polychrome brick patterning than the nave and crossing. The E window has a shafted rere arch with hood mould and embattled sill, above a band of relief foliage and ashlar alabaster wall (partly concealed by the later reredos). The step up to the chancel and 3 steps to the sanctuary incorporate Radyr stone treads, and the sanctuary has an encaustic-tile floor by Godwin of Lugwardine. The S side of the chancel has ashlar alabaster sedilia with cusped arches, gabled hoods with crocketed finials, and freestone shafts with moulded capitals and broad abaci. On the R side of the sedilia is a 2-bay arcade to the vestry and organ loft. A central octagonal pier has moulded capitals, 2 orders of chamfer, and hood mould with foliage stops. The outer responds are on pairs of shafts with head corbels, and have waterleaf capitals and square abaci. Below the organ pipes and behind the choir stalls is a subsidiary arcade of 3 cusped arches to each main bay, with castellated band above. The arcades have shafts, moulded capitals and broad abaci.
The Bute mausoleum has 2-bay arcades on the N side of the chancel and E side of the N transept. The transept arcade has an octagonal pier and polygonal responds, the chancel arcade has clustered shafts to the pier and responds, and both arcades have foliage capitals. The arcades are filled with a gilded wrought iron screen in a striking free Gothic style incorporating fleur-de-lys finials and 5-branch gasoliers. In the inner spandrel of the arcade to the transept is a mosaic of Christ in Glory. A 2-bay quadripartite vault has brick cells, the central ribs supported by ringed and filleted wall shafts with stiff-leaf capitals. The windows have richly detailed rere arches, including 2 orders of ringed shafts, with foliage moulding in the arches and hood moulds with head stops. Shields below the main lights are above the sills. The E window is flanked by empty canopied niches with tall pedestals.
The mausoleum has a mosaic floor, upon which are 7 sarcophagi of polished red Peterhead granite. These commemorate Charlotte Jane Windsor, Marchioness of Bute (1746-1800), John Stuart, first Marquess of Bute (1744-1814), Frances Coutts, Dowager Marchioness of Bute (1773-1832), John, Lord Viscount Mountstuart (1767-94), Gertrude Amelia Stuart (d 1809), Lord Henry Stuart (1777-1809) and Elizabeth Stuart (1819-22). Memorial slabs on the N sides of the sarcophagi are the original sealing stones from the previous mausoleum.
The mausoleum retains a complete scheme of stained glass figures by W.F. Dixon, of 1886. They represent name saints of those deposited in the mausoleum. In the N wall the L-hand window has figures of St Elizabeth of Hungary, Henry II, Holy Roman Emperor, and St Elizabeth of Portugal; the R-hand window has figures of SS Gertrude of Nivelles, John the Divine and Hemma; while in the E window are SS Charles Borromeo, John the Baptist and Francis of Assisi.
Other furnishings designed by Prichard include the font, which has a stepped plinth of Radyr stone, a round stem with detached alabaster shafts and foliage caps. The hexagonal bowl has inlaid alabaster crosses to the E and W faces. The rich polygonal alabaster pulpit stands on a freestone base, has thin shafts, inset panels with bosses, and foliage cornices with eagle book rest. The steps have a gilded wrought iron hand rail. The chancel is spanned by an alabaster dado with pierced roundels, on a freestone base. A wooden reredos of 1925 by Ninian Comper is in late medieval style with carvings by W.D. Gough and painting by H.A.B. Bernard-Smith. It comprises a central figure of the Risen Christ in a canopied niche with spirelet, flanked by apostles in canopied niches.
The transepts have memorial tablets in the W walls mainly reinstated from the earlier church. In the N transept is a sculpture of c1882 depicting St Margaret, placed there in 1980 and brought from St Margaret's House of Mercy in nearby Church Terrace. The choir stalls and communion rail are by A.D.R. Caroe, erected 1952-3. The firm of Caroe & Passmore designed a simple screen in the S aisle, installed in 1966. The nave and crossing retain original moulded pews.
Original leaded diamond panes by Saunders & Co survive in the porch and the sacristy E window. The E window was re-glazed in 1952 following damage to the previous window in the 1939-45 war. It was designed by Carl Edwards for James Powell & Sons, and depicts the Ascension, with Christ in Majesty to the upper lights. The E window of the N transept depicts St Margaret of Antioch, was designed by L.C. Evetts, and was installed in 1969 to replace an earlier bomb-damaged window. The remaining windows are mostly by Burlison & Grylls. In the S aisle are St Michael and St Simon the Cyrenian of 1916, and ladies engaged in charitable work of 1896, beneath a sexfoil window depicting an angel bearing a shield with the monogram 'PHC', for Philip Henry Coward, donor of many of the windows. In the nave S window is the Risen Christ of 1906. The W window, installed in 1920 to commemorate Howard's 50th wedding anniversary, shows the Transfiguration above scenes from the early life of Christ. In the nave N windows are the Archangel Raphael of 1896 and St German, the latter designed in 1891 by G.F. Bodley, architect of the church of St German in Roath. In the N aisle the W window shows the Revelation to St John, of 1917. The N windows show the 4 Latin doctors, of 1917, and SS Ambrose and Jerome, of 1890 and also designed by Bodley, beneath a sexfoil window of an angel bearing a shield with the monogram 'IEC' (Isabella Eleanor Coward).