Brady had five TD passes in the second quarter, a record for one period. The six touchdown throws tied Brady's own Patriots record. And the 59-point margin matched the largest since the NFL-AFL merger in 1970, the Los Angeles Rams' 59-0 win over the Atlanta Falcons in 1976.
The Patriots (4-2) gained a club-record 619 yards with Brady completing 29 of 34 passes for 380 yards.
The Titans (0-6) took their worst loss since they began play in 1960 as the Houston Oilers, eclipsing the 61-7 setback to Cincinnati in 1989. They won their first 10 games last season.
The white-and-powder-blue throwback uniforms the Titans wore to mark the 50th anniversary of the founding of the AFL may have been the only resemblance to that team that won that league's inaugural championship.
The Titans couldn't even stop New England when Brian Hoyer, a free agent rookie from Michigan State, took over for Brady on the second series of the third quarter with the score 52-0. He completed 9 of 11 passes for 52 yards in his pro debut and scored on a 1-yard run on his first series.
By that time, the wide empty spaces in the snow-covered stands matched the huge gaps in the Titans' defense that played without injured starting cornerbacks Cortland Finnegan and Nick Harper. Rookies started in their spots.
"You never go into a game thinking it's going to be like this," Patriots coach Bill Belichick said. "It's just our day today."
The Patriots led 10-0 after one quarter on a 45-yard run by Laurence Maroney and a 33-yard field goal by Stephen Gostkowski. Then came Brady's historic second quarter after five games of inconsistency.
In his sixth game since suffering a season-ending knee injury in last year's opener, his production for that quarter was remarkable even by his standards: touchdown passes to Randy Moss of 40 and 28 yards, to Kevin Faulk of 38 yards, and to Wes Welker of 30 and 5 yards.
Brady came back for the first series of the third quarter and threw a 9-yard scoring pass to Moss. Then Hoyer took over and scored on a 12-play, 61-yard drive that lasted 7:42.
In one 17-play stretch in the second quarter, the Titans gave up three scoring passes, lost two fumbles and an interception and even had a roughing-the-passer penalty on one of those touchdowns. One positive note: Collins threw his only completion of the first half in that miserable span.
He completed only 2 of 12 passes for minus-7 yards. Vince Young replaced him after Hoyer's touchdown and threw an interception, one of five Tennessee turnovers, on his first play. His only other pass was an incompletion.
Tennessee's defense was so bad that New England didn't punt until 4:13 remained in the game.
The Titans, whose 13-3 record last year was the NFL's best, have lost their last three games by 20, 22 and 59 points. They allowed Welker to catch 10 passes for a career-high 150 yards and Moss to get eight receptions for 129 yards.
A rare bright spot for Tennessee was Chris Johnson, who entered as the NFL's third leading rusher. He ran for 128 of the Titans' total of 186 overall.