In his career in first-class cricket (1865–1908), Grace scored 54,896 runs, registered 126 centuries (100 runs in a single innings), and, as a bowler, took 2,809 wickets. In 84 matches for Gentlemen versus Players he amassed 6,000 runs and took 271 wickets. In August 1876 he scored, in consecutive innings, 344 out of 546 for Marylebone Cricket Club versus Kent; 177 out of 262 for the Gloucestershire county team versus Nottinghamshire; and 318, not out, for Gloucestershire versus Yorkshire. In 1880 he was on the English team that played the first Test match against Australia in England. Late in life he could still handle a bat: in his last match, on July 25, 1914, when he was 66, his score was 69, not out, for Eltham.

The legend of Grace presents him as shaggy and ponderous, with a huge yellow cap atop a swarthy, bearded face. In his heyday, however, he possessed an athletic figure and was a swift runner. Although he practiced medicine, cricket was his life, to the extent that a biography (by A.A. Thomson, 1957) is entitled simply Great Cricketer. Of him, the famous bowler J.C. Shaw remarked: “I puts the ball where I likes, but he puts it where he likes.” His brother Edward Mills (1841–1911) was also a redoubtable cricketer.