'Jackpot' won back-to-back titles at Ally Pally in 2011 and 2012 but relinquished his crown last year as he lost out in an absolute classic to Michael van Gerwen in the quarter-finals.
After stretching his winning run at Alexandra palace to 15 matches, Lewis missed two darts at double top to beat van Gerwen before the Dutchman emerged with a thrilling 5-4 victory.
Lewis will still have happy memories at the venue though, and should have enough firepower to see off Smith, provided the veteran's awkward style and slow delivery does not upset the Stoke man's quick-fire rhythm.
The 1/16 favouritism for Lewis shows the gulf in class between the two, and a 3-0 scoreline (at 2/1) should be achievable but Smith is a former world semi-finalist, albeit 13 years ago, and with his style Lewis still needs to keep his concentration.
"I think that winning a third World Championship would really take me up to another level in the sport," said Lewis, who is a 5/1 shot to win the world title again with Sky Bet.
"To win it three out of four years would be massive too and I'm going to Alexandra Palace to do a job, to win the World Championship."
Justin Pipe also begins his campaign on Wednesday as he looks to go beyond the third round at Alexandra Palace for the first time, starting with a tie against Arron Monk.
World No 11 Pipe has been on the scene for a few years now and has been in two major semi-finals and one quarter-final this year, so is probably due a good run at the worlds.
Monk defeated Michael van Gerwen to win the World Under-21 Championship in 2011, but has not been able to follow the Dutchman's success on the main Pro Tour, which is reflected in Pipe being the heavy 2/9 favourite.
The evening gets underway with one of the most popular men on the circuit, Andy 'The Pieman' Smith taking on Steve Brown and looking to improve his poor record at the World Championship.
Smith has lost in the first round in five of the last six years, but Brown has not had much more luck with four first-round losses in his five appearances, but with some decent results at times this year his 11/10 could be the value here.
Youngster Michael Smith is also in action as he takes on the winner of the preliminary match between Morihiro Hashimoto and Paul Lim after just cracking the top 32 in the Order of Merit before the World Championship.
Smith, who is 2/9 to win his match, beat Ricky Evans in the final of the World Youth Championship, so after Evans' superb first round win it'll be interesting to see how his conqueror fares.
Catch all the darts action on Wednesday December 18 from 7pm on Sky Sports 2.