We present a search for quasi-monochromatic gravitational-wave signals from the young, energetic X-ray pulsar PSR J0537−6910 using data from the second and third observing runs of LIGO and Virgo. The search is enabled by a contemporaneous timing ephemeris obtained using Neutron star Interior Composition Explorer (NICER) data. The NICER ephemeris has also been extended through 2020 October and includes three new glitches. PSR J0537−6910 has the largest spin-down luminosity of any pulsar and exhibits fRequent and strong glitches. Analyses of its long-term and interglitch braking indices provide intriguing evidence that its spin-down energy budget may include gravitational-wave emission from a time-varying mass quadrupole moment. Its 62 Hz rotation frequency also puts its possible gravitational-wave emission in the most sensitive band of the LIGO/Virgo detectors. Motivated by these considerations, we search for gravitational-wave emission at both once and twice the rotation frequency from PSR J0537−6910. We find no signal, however, and report upper limits. Assuming a rigidly rotating triaxial star, our constraints reach below the gravitational-wave spin-down limit for this star for the first time by more than a factor of 2 and limit gravitational waves from the l = m = 2 mode to account for less than 14% of the spin-down energy budget. The fiducial equatorial ellipticity is constrained to less than about 3 ×10−5, which is the third best constraint for any young pulsar.