Polls indicated the election Sunday in North Rhine-Westphalia (NRW) could cost Merkel's coalition of conservatives and the pro-business Free Democrats the state legislature, and with it, their majority in parliament's upper house.
If the state's 13.5 million voters hand Merkel a defeat, it could hobble her seven-month-old alliance in Berlin by allowing the centre-left opposition to block planned tax and health care reforms for Europe's biggest economy.
The timing of the vote could hardly be worse for Merkel, coming just two days after parliament approved an unpopular rescue package for debt-stricken Greece, which Merkel described as essential to ensuring the euro's stability.
"The future of Europe and the future of Germany within Europe is at stake," she told lawmakers this week amid a media blitz to sell the package. "We are defending our currency."
A majority of voters oppose the €22.4 billion in emergency loans over three years to what they see as spendthrift Greece as Germany grapples with the parlous state of its own public finances.
But Merkel was also accused in Germany and abroad of dragging her feet over aid to Greece and thereby exacerbating the crisis. Sunday's vote is the first electoral test for Merkel since she clinched a second term in September. News weekly Die Zeit said that win or lose, the election would mark a crossroads for her.
"Angela Merkel may pass her zenith as chancellor on election night," it said. "Or she could find herself before a new beginning. There is little in between."
After months of falling popularity, polls this week showed the five-year-old centre-right coalition in the state could win 43 percent to 45 percent of the vote.
The rival Social Democrats (SPD), who held power in the state for four decades until 2005, and their preferred partners, the Greens, are scoring between 45 percent and 47 percent.
The SPD abstained in Friday's vote on the Greek loan package, a tactical move that analysts said could pay off in NRW. The tight race indicates that the next coalition could have any complexion, from centre-left to centre-right, with the parties scrambling in the days after the election to link up to form a ruling majority. The socialist Left party could be decisive in the arithmetic.
Initially discounted as a factor in NRW, polls now show a direct relationship between outrage over aid to Greece and slumping support for the conservatives.
Beyond Greece, voters are also unhappy with constant squabbling in the Berlin coalition, and NRW, home to the Ruhr industrial heartland, has suffered bitterly in Germany's worst post-war recession.
Also complicating matters is a "Rent-a-Rüttgers" scandal in which premier Jürgen Rüttgers' staff offered private conversations with him in exchange for donations of €6,000. He has denied knowledge of the practice.
The daily Financial Times Deutschland said Friday that it would not be a catastrophe if a centre-right defeat in NRW put the brakes on Merkel's decidedly modest reform agenda.
"But things would become dangerous if the rescue package for Greece is not enough to end the eurozone crisis," it wrote.