Spurs were held by a dogged performance from Vladimir Petkovic's side as the two heavyweights of Group J settled for a point apiece in their Europa League opener
The American, making his full debut, connected with a Gareth Bale cross but was adjudged offside, before Caulker rose at the back-post in the second period, only to see his header ruled out for a foul on Stefano Mauri.
Andre Villas-Boas gave full debuts to Hugo Lloris and Dempsey as well as handing Caulker his first start of the season while Aaron Lennon captained a strong Spurs team.
Tottenham began the game brightly, confident in possession in front of a Lazio team happy to feel its way into the fixture and although the hosts tentatively prodded at the Italians, it was Vladimir Petkovic's team that created the first opportunity of the match.
Kyle Walker's lax header relinquished possession in his own half, allowing Christian Ledesma to play his left back Senad Lulic in behind. The Bosnian's first-time cross to an unmarked Miroslav Klose looked an inevitable goal but the 34-year-old fluffed his lines, missing the ball under pressure from Lloris.
This sparked the north London side into action and Lennon latched onto a neat pass from Jermain Defoe but saw his pass to Bale intercepted, before a second cross had the Welshman force Federico Marchetti to tip over the bar.
Just after the 20th minute, Dempsey was denied a maiden goal by the linesman's flag as he nodded an excellent cross from Bale into the back of the net. Though it looked close, on reflection, the Texan was ever so slightly offside.
The game was finely poised and although it lacked creativity at times, Lazio was never the whipping boy. Three minutes before halftime Jan Vertonghen's defensive clearance was walloped back at goal on the volley by Alvaro Gonzalez, and despite beating Lloris, the crossbar prevented the Uruguayan opening the scoring.
The referee rather oddly blew the halftime whistle 30 seconds before the full 45 minutes had been played, but in a half that occasionally lapsed into procession, it had a bizarre logic.
There were no changes for either side at the break and in what was a noticeably quicker resumption to play, Tottenham carved the first clear-cut chance.
Defoe, who had linked play well with the midfield behind him, drifted into the right channel and as he took Andre Dias, the center back, with him, cut inside and rolled Lennon in on goal. The winger took an unnecessary first touch, where a shot looked the better option, but his blocked shot and the ensuing bundle almost landed in the Lazio goal under pressure from Dempsey.
However, the Biancocelesti survived but again had to thank the linesman minutes later for flagging for offside as Bale rolled the ball into Defoe for a tap-in.
As the game wore on, the Italian outfit began snapping at the heels of Bale and Lennon and collected a handful of bookings. From one such resulting free kick, Sandro really should have given Spurs the lead but his header lacked clarity and skidded past the far post.
And set-pieces began to prove the home side's best chance of taking the lead. Firstly Dempsey was rugby tackled by Klose in the box before Caulker saw his planted header from a corner ruled out by the referee for a fairly innocuous collision with Mauri.
With 15 minutes to play, Gylfi Sigurdsson was introduced for Dempsey as Villas-Boas chased a late winner but Petkovic's side slowed the tempo with intelligent use of the dark arts.
Yet, there was one final chance for Spurs as substitute Andros Townsend stole in unmarked at the back post, but his header lacked conviction and direction, bouncing out for a goal kick, leaving Bale and Co. frustrated figures in the centre of the six-yard box.
All in all, it was a display that didn't quite live up to its billing, as the clash between two clubs that share a sentimental history ultimately, underwhelmed. That said, as the two heavyweights in Group J, sharing the spoils cannot be sniffed at and there were certainly positives to take to the weekend as Villas-Boas targets his first home victory.