The American world number one Williams stormed past defending champion Agnieszka Radwanska in the semi-finals, dropping just three games as she continued her dominance in Miami.
Williams has been relentless in her march through the draw and was in inspired form again on Thursday, as Radwanska put it in her post-match interview, it "doesn't even matter who's on the other side of the net when she plays like that".
The final would therefore seem somewhat of a formality, but Serena will come up against the most difficult challenge she could possibly face in Sharapova.
The Russian world number two has also been ruthless in Miami, even surpassing Serena's feats having not dropped a single set thus far. She dispatched of Jelena Jankovic in her semi-final tie in just over an hour, losing just three games.
It extended an incredible run for the third seed, who has now won 11 straight matches as well as 22 straight sets, perhaps playing some of the best tennis of her career to date.
Sharapova is just a solitary win away from becoming only the third woman to ever pull off the Indian Wells-Miami double, following in the footsteps of Steffi Graf and Kim Clijsters.
However the Russian has reached the final of this event four times previously, ending on the losing side on all four occasions including the last two years consecutively.
Historically, her head-to-head record with Williams also suggests that a struggle lies ahead, with the American winning 11 of their 13 meetings, including the last 10. The pair met just last month in Doha, with Serena completing a 6-3 6-2 win.
Despite Sharapova's outstanding current form there is no doubting that Williams has the edge and she'll know how to exploit her opponent. She made it five straight wins against Radwanska, and she will again be fully aware of how to pick apart her opponent's game.
Serena is a strong favourite at [1.39] to deny Sharapova's bid to make history, simultaneously writing her own name in the history books with yet another success in Miami. However, the real value lies elsewhere.
In their last five meetings, Sharapova has hardly even been able to challenge her rival, losing in straight sets each time. Therefore the Under 20.5 games market looks attractive as well as another demoralising straight sets defeat for the Russian.
Williams has looked focused and composed, and for all of Sharapova's best efforts she could well be looking back on a hat-trick of losing final appearances in Miami come Saturday night.