Answer by taking a quote from the following article:

Sam & Dave were an American soul and R&B duo who performed together from 1961 until 1981. The tenor (higher) voice was Sam Moore (born 1935) and the baritone/tenor (lower) voice was Dave Prater (1937-1988). Sam & Dave are members of the Rock and Roll Hall of Fame, the Grammy Hall of Fame, the Vocal Group Hall of Fame, the Memphis Music Hall of Fame, and are Grammy Award and multiple gold record award-winning artists.

When Sam & Dave arrived at Stax, they worked with producer & engineer Jim Stewart and songwriters including the MGs' guitarist Steve Cropper, who wrote or co-wrote four of their first eight recordings. The duo then moved to relative newcomer writers and producers Isaac Hayes and David Porter. Hayes and Porter wrote and produced the duo's biggest hits (although they did not receive production credits until the Soul Men LP and singles). According to Moore and Prater, they also greatly influenced the duo's singing style, and shifted their recording style from the style of their Roulette records to a more live, more energetic gospel, call-and-response feel and beat driven soul style the group is known for today.  Sam & Dave's Stax records also benefited from the musicians and engineering at Stax. The Stax house band, Booker T. & the M.G.'s, and the Stax horn section, the Mar-Keys, were world-class musicians who co-wrote (often without credit) and contributed to recordings--the same musicians who recorded with Otis Redding, Wilson Pickett, Carla Thomas and other soul artists. Sam & Dave's Stax recordings through 1967 were engineered by Stax founder Jim Stewart, who created the Memphis Sound by recording live in a single take. Stewart is credited for instrumental mixes that allowed for instrumental separation and the distinct contribution of each instrument to the overall feel of the song.  While the first two Stax singles failed to chart, the third, the Hayes/Porter composition (with similarities, including the title, to a gospel standard) "You Don't Know Like I Know" hit #7 R&B in 1966. This was the first of 10 consecutive Top Twenty R&B chart hits over three years, and 14 R&B chart appearances during their career.

What was their most popular song?
This was the first of 10 consecutive Top Twenty R&B chart hits over three years, and 14 R&B chart appearances during their career.