In small amateur telescopes, M53 appears as a slightly oval nebulous object with a large, bright center, of rather even surface brightness and evenly fading out to the edges. Mallas reports that he saw many stars in the 4-inch refractor under excellent viewing conditions, with the central part appearing somewhat grainy. In somewhat larger telescopes, its outer fringes appear resolved into stars, while the central part is still unresolved and grainy, with one star standing out, in telescopes of about 8-inch aperture. Large instruments of about 12-inch up show it well resolved, with a moderately concenterated nucleus and stars spread out to about 12 arc minutes diameter.

M53 can be easily found just 1 deg NE of the 4th-mag star, 42 Alpha Comae Berenices, a visual binary star (A: 5.05, B: 5.08, both of spectral type F5V). Alpha Comae itself may be located by either following the line from Arcturus via Eta Bootis by a further 11 deg to the W, or by following the line of Gamma - Delta - Epsilon Virginis by another 7 deg NNE.