Lofton scorched Georgia's zone defense, scoring 19 of his 22 points in the second half, and No. 4 Tennessee held on for a 74-71 win over the Bulldogs on Saturday.
Lofton made five of seven 3-pointers after halftime, and the Vols survived when Sundiatta Gaines, who scored 23 points, missed a last-second 3.
Smith scored only two points on 1-for-7 shooting, one game after he set a career high with 32 in a win over Arkansas.
"It's as simple as this, there is no other two-player combination in the country that is as excellent at making outrageous, spectacular shots, defended, deep-range shots, as those guys," said Georgia coach Dennis Felton of Lofton and Smith. "They're very, very difficult to deal with."
Lofton, a senior, increased his Southeastern Conference career record for 3-pointers to 398 with his six against Georgia, which tried to cover for a shortage of players by sticking to a zone defense.
"I got in a rhythm at the beginning of the second half," Lofton said. "I got great open looks and it just kept happening."
Tennessee (23-2, 10-1) has the best 25-game record in school history and has won eight straight in the series with Georgia (12-11, 3-7), including a sweep of this season's two games.
Lofton was 1-of-6 from 3-point range at the intermission before scoring 19 of his team's 39 second-half points.
"That's why he's an All-American," Tennessee coach Bruce Pearl said. "No question, Chris Lofton willed this win. Chris Lofton put this team on his shoulders in the second half. We were not going to leave this building without a win, and Chris Lofton saw to that."
Gaines, who also had nine rebounds and eight assists, played the full 40 minutes and helped keep Georgia close.
Georgia was playing its third straight game without suspended starting guard Billy Humphrey following his arrest for underage drinking. Gaines moved from point guard to fill in for Humphrey and scored 32, 27 and 23 in the three games.
"Yada is a terrific player," Pearl said of Gaines. "He is in control of that offense and of that entire team. ... We felt like we were in control and even though we went up by 10 a few times, we never felt them dying down or going away."
Humphrey is cleared to return for Georgia's next game at Kentucky on Tuesday night, according to Felton, if his sore knee allows.
Terrance Woodbury added 14 points for Georgia.
With Tennessee leading 74-71, Woodbury missed a 3-pointer with 47 seconds left.
Chism missed a layup with 17 seconds left, but Woodbury was short on another 3 from the corner with less than 10 seconds left.
Gaines couldn't make a last-second 3-point try after missing a free throw, grabbing the rebound and racing to the corner for the shot. The errant 3 hit the rim twice before falling away.
The finish was much different than Tennessee's 85-69 win in Knoxville on Jan. 26, but Pearl noted Georgia was 11-2 at home.
"I'm not going to come to Georgia and get a road win and complain about it," Pearl said.
"A huge factor in the outcome was their depth advantage," Felton said. "They were able to just keep rotating in fresh bodies and most of our guys played the last part of the game exhausted."
Chism had 14 points as Tennessee took a 35-31 halftime lead despite 1-for-9 shooting on 3-pointers.
Georgia took the lead with a run early in the second half. Woodbury's 3-pointer, followed by Gaines' steal and three-point play, helped the Bulldogs take a 49-45 lead. A jumper by Zac Swansey, who had 10 points, gave Georgia a 51-48 lead.