What is the worst thing that ever happened to your vehicle during a long road trip? ~

Burned out a wheel bearing.
Christmas Eve, 2014. My mother lay dying in a palliative care hospital in Springwood, about 70 miles west of Sydney. The trip from Adelaide is a little over 1000 miles.  Just past halfway, the car felt a little "off", but there was no possibility of stopping, the likelihood of any accommodation being vacant, or repairs being possible, in any of the country towns along the way was next to nothing at that time of year and I couldn't risk any delay before I'd told her goodbye. By the time I got to the hospital the car was shaking violently every time I turned left.
After hours on Christmas Eve (a Wednesday). No mechanic services open, no hire car services open, after seeing Mum (unable to speak and heavily sedated, but she did press my hand faintly - a herculean effort) I called the NRMA. They told me I had to leave the car where it was, they'd tow it to a mechanic on the following Monday - the family and I had to catch a train to St Clair (a rough area in Sydney's outer west), in which was the nearest motel with a 3 day vacancy, until a hire car would become available on Saturday.
The accommodation and temporary car hire was covered (it pays to have premium membership in my state's auto association, I only had to pay for fuel), the repairs weren't. Neither was a new bearing available before New Year, I couldn't wait that long so I had to settle for a used one. Over $1000, mostly labour.

1. Interstate 10, FL. The ignition points in the distributor closed, thus no spark was created for the plugs. Loose screws. I fixed it with a screwdriver.
2. Alternator failure in a thunderstorm on a Sunday. I found an auto parts store just closing up. He gave me a break and sold me one. Replaced it in the rain.

I left it home.  Poor thing "cried" oil for months, and the battery just... died.

The Chauffeur had to keep stopping  to get more booze. This post was edited by ONeg-84 at July 15, 2021 7:10 AM MDT

The only time I had a problem on a road trip when I had to stop at a motorcycle shop in South Dakota to have the front tire of my motorcycle changed. My friend and I were on our way to the Sturgis motorcycle rally. It took only a couple of hours so it wasn't much of an inconvenience. We covered a lot of miles and saw some beautiful scenery. :)

Fuel pump...Grand Canyon. 

This post was edited by Thriftymaid at July 22, 2021 2:20 PM MDT

The generator stopped working while I was driving on a foggy night over a mountain pass.  The lights quit working so I drove with the drivers side door open enough to see the line down the middle of the road.  It was the only way not to go over a cliff.  The fog was so dense I could not see the side of the road for a safe place to pull over. 

I had an engine throw a rod on a trip. We sold the entire car to the junk yard for $10


This post was edited by my2cents at July 22, 2021 2:20 PM MDT

Our fuel pump went out when we were driving on the interstate from the Chicago area back to Central IL.  Luckily, we found that our car had 2 fuel pumps so we were able to driving carefully about 10 miles to the nearest dealer to have the one that failed repaired.

When we were first married, we had 2 cars.  The first one's water pump went out.  My husband planned to take our other car to work until we could get it fixed.   When he started the second car ... THAT water pump went out!  Hard to imagine 2 different models/years cars with the same problem.  :)