Shares of CSX tumbled 10.7pc and were set for their biggest one-day drop in nearly 17 years, after the company posted lower-than-expected quarterly profit and cut its full-year revenue forecast.
Rival Union Pacific Corp slipped 5.7pc, weighing heavily on the benchmark S&P 500 while Kansas City Southern fell 4.4pc. Both companies will report results this week.
Losses in CSX also pushed the Dow Jones Transport Average down 3.15pc. The S&P 500 industrials, with a 1.62pc decline, was the top loser among the 11 main sectors.
Since a sharp fall in May, Wall Street's main indexes have trended higher to hit record highs on hopes that the Federal Reserve would cut interest rates at its policy meeting at the end of this month.
The market's recent run-up on optimism around a Fed rate cut is likely why there is somewhat of a breather now, said Barry James, chief investment officer of advisory firm James Investment Research in Alpha, Ohio, adding that trade tensions remained an overhang.
"There's still a lot of risk in the market, like massive amounts going into passive rather than active managers and valuations being elevated, so we could run into potholes as we did back in December and May," James said.
At 12:29 p.m. ET, the Dow Jones Industrial Average was down 56.40 points, or 0.21pc, at 27,279.23, the S&P 500 was down 8.78 points, or 0.29pc, at 2,995.26. The Nasdaq Composite was down 8.45 points, or 0.10pc, at 8,214.35.
Abbott Laboratories rose 3.7pc after the medical device maker topped quarterly profit estimates and lifted its full-year adjusted earnings forecast.
Bank of America Corp rose 1.6pc after posting a profit beat, but the lender lowered its annual net interest income forecast.
This follows similar warning signs from JPMorgan Chase & Co , Citigroup Inc and Wells Fargo & Co, which reported a dip in margins and stoked fears of interest rate cuts pressuring profit.
Profit for S&P 500 companies is expected to rise 0.4pc in the second quarter from a year ago, according to Refinitiv IBES data. Of the 43 companies in the S&P 500 that have reported so far, 83.7pc have beaten analysts' estimates.
Qualcomm Inc rose 1pc after the US Justice Department asked a federal appeals court to pause the enforcement of a sweeping antitrust ruling against the mobile chip supplier.
The Philadelphia Semiconductor index rose 0.49pc, also helped by strong quarterly profit from Dutch chip equipment maker ASML Holding NV .
FAANG member Netflix Inc and blue-chip technology company International Business Machines Corp were marginally lower ahead of their results due after the bell.
Declining issues outnumbered advancers for a 1.47-to-1 ratio on the NYSE and a 1.39-to-1 ratio on the Nasdaq.
The S&P index recorded 24 new 52-week highs and one new low, while the Nasdaq recorded 45 new highs and 71 new lows.