The main bus station is on Calzada de la Estación, a 20-minute walk from the Parroquia — though the walk is uphill.
There are direct buses from here to Querétaro, Guadalajara, Mexico City, and elsewhere. Primera Plus is very nice and comfortable, and ETN is like flying first class (with none of the hassle of checking bags or airport security).
You can catch taxis right outside the door, or Ubers at the stop up a small set of stairs just beyond the taxi stand.