Mathematica owes much of its lineage to Macsyma, a computer algebra system that really was Lisp on the inside; its spiritual descendant, Maxima, is written in CL.
Wolfram and Chris Cole started developing a symbolic math system, which they named Symbolic Manipulation Program (SMP), when they found that Macsyma was unable to handle the computational needs for their physics research. For problems that they considered to be medium problems, Macsyma could do the work, but it was very slow. For problems that they considered to be large problems, Macsyma ran out of memory. Thus, they needed something more efficient in both time and space.
Wolfram and Cole planned on writing in C. They asked researchers in the symbolic computation community about this, and were told that it was a terrible idea. C was too low level. To do a high level system like a symbolic algebra system, you had to work at a much higher level. Using anything less than Lisp pretty much guaranteed your project would take forever.
Wolfram and Cole decided on C anyway. (BTW, C at CITHEP was not quite standard C. Norman Wilson had hacked the compiler to handle float and double expressions the same way FORTRAN handled them, making C almost as good as FORTRAN for numerical work, and C had mostly taken over from FORTRAN for physics computation there).
I recall seeing the factor of 100 number, or something like that, in one of the first public presentations of SMP. On the research problems that Wolfram and Cole considered to be medium sized, SMP was beating the Lisp-based systems by around a factor of 100.