Previous matches in Tbilisi and Moscow were relative cakewalks in comparison to the 2,742-mile round trip to the communist state of Transnistria.
Moldovan champions Sheriff Tiraspol impressed throughout last night's Group K clash, although Vertonghen gave Spurs some breathing space with a 12th-minute opener.
Henrique would have levelled almost immediately were it not for Vlad Chiriches' block, while Cadu, Ismail Isa and Ricardinho also came close for the hosts.
Jermain Defoe eventually wrapped up a 2-0 win with a strike that equalled Martin Chivers' club record of 22 European goals, leaving Vertonghen relieved.
"It's the best team we've played so far this season in the Europa League, so it's a good result for us," the Belgium international said at Stadionul Sheriff.
"It wasn't our best game but we kept a clean sheet and we won a difficult away game, so we can be happy.
"It was nice because I haven't scored this season, so it's good to have my first goal."
Vertonghen's goal was somewhat overshadowed, though, by Defoe's record-equalling, but slightly deflected, second-half strike.
"It is some achievement," Spurs boss Andre Villas-Boas said. "If we continue like this, there is a big chance he will break the record.
"It will be another great achievement for him. I am sure he will achieve it.
"Let's not celebrate it before it happens, but it will be a great record for him and the club. It was another great performance by Jermain."
The victory at Sheriff leaves Spurs top of Group K with maximum points and with five clean sheets from as many games in the Europa League this season.
They could have secured their place in the last 32 on Thursday night, but Anzhi's 1-0 defeat of Tromso means they will have to wait for Sheriff's trip to White Hart Lane on November 7.
"It was not easy," Villas-Boas added. "I think we deserved to take the lead but they counter-attacked extremely dangerously.
"We also had a lot of chances and could have gone 2-0 up comfortably.
"In general, we did enough to win the game and get to nine points, which was the objective so we can achieve qualification at the next game."